Parenterally for prevention and treatment of carnitine deficiency in patients with end-stage renal disease undergoing dialysis (dialysis-related carnitine disorder);1710 designated an orphan drug by FDA for this use.6

Effects of supplemental carnitine on manifestations of carnitine deficiency and on clinical outcomes in patients with end-stage renal disease undergoing dialysis not determined.1811

Carnitor Dosage and Administration

General

Secondary Carnitine Deficiency Associated with an Inborn Error of Metabolism.

Some experts recommend evaluating clinical response at 3-month intervals following initiation of drug, considering dosage adjustment to lowest effective dosage once desired outcome for specific manifestation has been attained, and discontinuing drug if clinical improvement has not occurred within 9–12 months.7

Administration

Administer orally (as a solution or tablets), by direct IV injection, or by IV infusion.12

Oral Administration

Solutions may be administered alone or dissolved in beverages or other liquid foods to reduce taste fatigue.2 Slowly administer solution in evenly spaced doses throughout the day (i.e., at least 3 or 4 hours apart), preferably during or following meals, to maximize tolerance; adverse GI reactions may result from rapid administration of solution.2

Rate of Administration

Carnitine deficiency in patients with end-stage renal disease undergoing dialysis, direct IV injection: Slowly over 2–3 minutes into the venous return line after each dialysis session.1

Dosage

Decreasing the dosage of oral levocarnitine may diminish or eliminate drug-related patient body odor or GI symptoms if present.211

Pediatric Patients

Primary Systemic Carnitine Deficiency

Oral

Pediatric patients (≤18 years of age): Initially, 50 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.23 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range is 50–100 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart), up to a maximum total daily dosage of 3 g.23

Exact dosage based on clinical response.2 Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

Secondary Carnitine Deficiency Associated with an Inborn Error of Metabolism

Oral

Pediatric patients (≤18 years of age): Initially, 50 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.23 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range is 50–100 mg/kg daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart), up to a maximum total daily dosage of 3 g.23

Exact dosage depends on clinical response.2 Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

IV

Pediatric patients (≤18 years of age): 50 mg/kg every 3 or 4 hours administered by slow, direct IV injection over 2–3 minutes or by IV infusion; do not administer less frequently than every 6 hours.13 Subsequent total daily dosage of approximately 50 mg/kg, adjusted as required and given in divided doses (i.e., every 3 or 4 hours), is recommended.1

In pediatric patients (≤18 years of age) with severe metabolic crisis, a loading dose has often been administered, followed by an equivalent dose over the following 24 hours.13 These patients underwent close supervision and monitoring of plasma levocarnitine concentrations, with subsequent dosage adjusted accordingly.3 In individual case reports, highest total daily dosage administered has been 300 mg/kg.13

Initiation of therapy may be prompted by trough (i.e., predialysis) plasma levocarnitine concentrations that are below normal (40–50 mcmol/L).1

Adjust dosage based on trough (i.e., predialysis) plasma levocarnitine concentrations; dosage reductions (e.g., to 5 mg/kg after dialysis) may be initiated as early as the third or fourth week of therapy.13

Adults

Primary Systemic Carnitine Deficiency

Therapy with Levocarnitine Tablets

Therapy with Levocarnitine Oral Solution

Oral

Initially, 1 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.23 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range for a 50-kg patient is 1–3 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart).23

Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

Secondary Carnitine Deficiency Resulting from an Inborn Error of Metabolism

Therapy with Levocarnitine Tablets

Therapy with Levocarnitine Oral Solution

Oral

Initially, 1 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart); slowly increase dosage while assessing tolerance and therapeutic response.23 (See General and also Administration, under Dosage and Administration.)

Usual recommended dosage range for a 50-kg patient is 1–3 g daily, given in 2 or 3 divided doses (administer each dose at least 3 or 4 hours apart).23

Administer increased dosages with caution and only when clinical and biochemical considerations make it seem likely that increased dosages will be of benefit.2

IV

50 mg/kg every 3 or 4 hours administered by slow, direct IV injection over 2–3 minutes or by IV infusion; do not administer less frequently than every 6 hours.13 Subsequent total daily dosage of approximately 50 mg/kg, adjusted as required and given in divided doses (i.e., every 3 or 4 hours), is recommended.13

In patients with severe metabolic crisis, a loading dose often has been administered, followed by an equivalent dose during the following 24 hours.13 These patients underwent close supervision and monitoring of plasma levocarnitine concentrations, with subsequent dosage adjusted accordingly.3 In individual case reports, highest total daily dosage administered has been 300 mg/kg.13

IV

Initially, 10–20 mg/kg of dry body weight administered by slow, direct IV injection over 2–3 minutes into the venous return line after each dialysis session.1

Initiation of therapy may be prompted by trough (i.e., predialysis) plasma levocarnitine concentrations that are below normal (40–50 mcmol/L).1

Adjust dosage based on trough (i.e., predialysis) plasma levocarnitine concentrations; dosage reductions (e.g., to 5 mg/kg after dialysis) may be initiated as early as the third or fourth week of therapy.1

Cautions for Carnitor

Contraindications

Warnings/Precautions

Specific Populations

Pregnancy

Lactation

Distributed into milk in cows; not known whether levocarnitine distributes into human milk.12 Consider discontinuance of nursing or the drug.12

Pediatric Use

Dosage of levocarnitine in pediatric patients ≤18 years of age was based on specific patient case record observations rather than on studies that specifically defined age by protocol.123

Renal Impairment

Safety and efficacy of oral levocarnitine not established in patients with renal impairment.12

Chronic administration of high doses of oral levocarnitine in patients with severely compromised renal function or in patients with end-stage renal disease undergoing dialysis may result in accumulation of potentially toxic metabolites, trimethylamine (TMA) and trimethyloxamine (trimethylamine-N-oxide [TMAO]), since these metabolites are normally excreted in urine.1237

Safety of IV levocarnitine has been established in patients with end-stage renal disease.13

Extent

Plasma Protein Binding

Elimination

Metabolism

Metabolized principally to TMAO and γ-butyrobetaine in GI tract by bacteria.12457

Elimination Route

In healthy adults, approximately 9% of dose excreted in urine as levocarnitine (uncorrected for endogenous urinary excretion) following oral administration.123

Approximately 58–65% of a dose excreted (as levocarnitine and metabolites) in urine and feces in 5–11 days following oral administration of radiolabeled drug to patients receiving a high carnitine diet and additional carnitine supplements for 15 days.1235 About 4–8 and <1% of administered radiolabeled dose excreted in urine as levocarnitine and in feces as total carnitine, respectively.1235 TMAO principally excreted in urine (8–49% of administered radiolabeled dose) and γ-butyrobetaine principally excreted in feces (0.44–45% of administered radiolabeled dose).1235

Approximately 76% of dose excreted in urine within 24 hours following direct IV injection.12

Actions

May promote excretion of excess organic or fatty acids in patients with defects in fatty acid metabolism and/or specific organic acid metabolic disorders that result in accumulation of acyl-coenzyme A (acyl-CoA) esters.12

In patients with secondary carnitine deficiency, eliminates acyl-CoA compounds by promoting formation of acylcarnitine, which is quickly excreted.12410

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